Multimodal evaluation for predicting myocardial fibrosis and ventricular arrhythmias in patients with mitral valve prolapse: limited utility of clinical, echocardiographic and CMR parameters

Abstract Background Mitral valve prolapse (MVP) has been associated with ventricular arrhythmias (VAs) in a small subset of patients. Myocardial fibrosis, typically detected as late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR), is supposed to be the potential arrhythmogenic substrate. It remains unclear which MVP patients, identified by transthoracic echocardiography (TTE), should be referred for CMR to evaluate for LGE. At present, no combination of clinical or imaging parameters reliably predicts LGE or the occurrence of significant VAs. Purpose The objectives of this study were: (1) To assess whether and which demographic, clinical, ECG, Holter, and TTE parameters are associated with the presence of LGE by CMR in patients with MVP; (2) to evaluate whether and which demographic, clinical, ECG, TTE, and CMR features predict significant VAs. Methods This monocentric study has a prospective and retrospective design. All patients underwent a standardized assessment including clinical history and examination, resting ECG, 24h-ECG Holter monitoring, TTE, and CMR. Significant VAs were defined as ≥ mild VAs (≥ 5% premature ventricular beats on 24h-ECG Holter and/or documentation of non-sustained ventricular tachycardia) according to the recent Consensus 1. Besides standard TTE parameters, we assessed mitral leaflet thickness, presence of bileaflet prolapse, mitral annular disjunction (MAD), Pickelhaube sign, and systolic curling of the left ventricular (LV) basal lateral wall (Figure 1). The CMR protocol included LGE evaluation, T1 and T2 mapping, and extracellular volume (ECV) mapping for myocardial tissue characterization. Results A total of 138 patients were enrolled in the current study. Patients with LGE (LGE+; n=55, 39.9% of the overall population) showed a higher prevalence of MAD on TTE compared to those without LGE (LGE-) (Figure 2). No other significant difference in clinical, ECG, Holter or imaging parameters was detected between the two groups, except for a trend toward higher prevalence of MAD at CMR in LGE+ patients (76.4% in LGE+ vs. 62.7% in LGE-; p=0.09). Patients with significant VAs (n=43) did not differ significantly from those without significant VAs (n=95) in terms of family or clinical history, physical exam findings, pharmacologic therapy, ECG parameters, or imaging features on TTE and CMR. No significant difference was observed in significant VAs’ occurrence even when patients were stratified according to the presence of MAD alone, LGE alone, or both. Conclusions Despite the limited sample size, our findings appear to support the "Padua Hypothesis" 2, which suggests that MAD is associated with mechanical stretch of the myocardium, which in turn induces fibrosis in the LV lateral wall. However, these data highlight the current limitations in clinical practice in identifying MVP patients at risk for significant VAs, suggesting the need for further studies to identify reliable predictors of VAs.Multimodal Imaging of MVP